CN101037654B - Spotter with spot pattern encryption function and detection device for coping with spot pattern encryption - Google Patents

Spotter with spot pattern encryption function and detection device for coping with spot pattern encryption Download PDF

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Publication number
CN101037654B
CN101037654B CN2007100918047A CN200710091804A CN101037654B CN 101037654 B CN101037654 B CN 101037654B CN 2007100918047 A CN2007100918047 A CN 2007100918047A CN 200710091804 A CN200710091804 A CN 200710091804A CN 101037654 B CN101037654 B CN 101037654B
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probe
pattern
fixed substrate
substrate material
solid phase
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CN101037654A (en
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石桥亨
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Canon Inc
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Canon Inc
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Abstract

A spotter spots a plurality of probes specifically binding to target materials in a plurality of spot regions on a substrate. The spotter comprises a spotting unit which spots each probe according to the spot position pattern; and a spot position pattern encoding unit for encoding the spot position pattern according to the certain information in each probe fixing substrate to be formed.

Description

Have the placing machine of dot pattern encryption function and the proofing unit corresponding with this encryption
Application of the present invention is that application number is 200410059741.3, the applying date is on June 18th, 2004, denomination of invention is divided an application for the patented claim of " having the placing machine of dot pattern encryption function and the proofing unit corresponding with this encryption ".
Technical field
The present invention relates at microarray, DNA chip etc., have in the body material that can carry out a plurality of probes of special bonded, the solid phase carrier subject substances, be used for the fixed operation of a plurality of probes placing machine (spotter), be fixed with proofing unit that the fixing base material of a plurality of probes uses and a plurality of probes that used by placing machine carried out the dispenser that branch is annotated.
Background technology
As the probe fixed substrate material that can be fixed on solid phase carrier or substrate material surface, can enumerate out the DNA chip to a plurality of probes of the special bonded of subject substances (probe).So-called DNA chip is to use probe as hybrid reaction, is arranged in solid phase surface to a plurality of dna segments or oligonucleotide with different bases arrangements, with the dna probe array of fixing of high-density.As the dna probe that is fixed on such DNA chip, be chosen in and analyze genetic discovery, variation, the effective base permutation and combination in aspect such as polymorphic simultaneously.
As the method that on solid phase surface, is fixed as nucleic acid molecule array-like, for example at USP the 5th, 688, disclose in No. 642 specification sheetss through solid phase synthesis, use photoetching to be made as the solid phase oligonucleotide array that required base is arranged to oligonucleotide.And the making method of using ink jet method to lay the dna molecular of making in advance (spot) the solid phase dna probe array to the solid phase surface is being disclosed in International Publication the 95/25116th trumpeter's volume, the 5th, 688, No. 642 specification sheetss of USP.
In addition, in detection treatment step, generally contact subject substances with the probe of solid phase probe array, form special complex body between the two with signizations such as fluorescent substances based on the subject substances of probe hybrid reaction.This hybrid reaction normally contacts solid phase dna probe array or be immersed in and makes in the subject substances dissolved solution; One side heats one in the face of probe; Form the reaction of the special complex body of subject substances, this moment, reaction conditionss such as concentration or temperature were according to the combination of probe and subject substances and different.Use proofing unit such as fluoroscopic examination machine to observe and derive from the fluorescent substance that in the signization of subject substances, uses in advance, confirm the having or not of probe and subject substances bonded complex body (mixtinite), its growing amount etc.
It is said to open the 2002-101878 communique like the spy, and this DNA chip also can use in the gene diagnosis.
The actual gene diagnosis of in diagnosis, using comprises and results' (information) such as the having or not of the genetic information corresponding compound bodies of each patient's inherent (mixtinite), growing amount with the DNA chip; For example in the DNA chip that uses fluorescence labelling; Do not identify as radioactive element; Therefore the decay along with effluxion of identification capability, has the advantage that can read result's (information) repeatedly.And because can read result's (information) repeatedly, so if the diagnosis of using in the diagnosis with DNA chip and this patient's name leakage, even then the third party also can know this patient's diagnostic result.
Certainly in medical institutions such as hospital, in order not leak the information that is documented on the case card etc. to the third party, advanced best endeavors for each patient, take secrecy provision.And in hospital etc., usually entrust outside dealer to carry out this waste treatment as Biohazard Waste with proper process facility the utensil, the test tools made that use in the diagnosis.
It should be noted that; In the stage of the waste treatment of entrusting to this outside dealer, that yes is complete to the leakage of outside, lost physical management state to avoid satisfying " pathogenicity bo material " etc. that possibility is adhered in the existence of the benchmark of each Biohazard Waste regulation.But in the process of this waste treatment, fully realize management, but, have the tendency of not too noting constantly for management to " information " residual on the DNA chip that uses in the diagnosis to " leakage physically ".For example, in the management of " leakage physically " was divided, if the third party can read " information " residual on the DNA chip that uses in the diagnosis once again, even then itself do not take the outside to the DNA chip, " information " also might leak into the outside.Therefore, carrying out aspect the more high-grade security management, residual " information " is leaked to the outside on the DNA chip even just need, and also can't make this " information " and patient's diagnostic result connect such technology simply.
For example; The base arrangement that constitutes each dna probe of DNA chip is to be difficult to analyze with the DNA amount that is present on a slice, still from untapped a plurality of DNA chips, each dna probe of Separation and Recovery; If become the DNA amount of a great deal of, just might analyze this base and arrange.Arrange if promptly decipher the base of the dna probe that constitutes the DNA chip, just can judge what kind of diagnostic result is residual " information " be equivalent on the DNA chip that uses in the diagnosis.If distinguish that this DNA chip that uses in the diagnosis is in which patient's diagnosis, to use, the diagnostic result that the result will take place by this patient leaks into outside incident.
Therefore, even prepared a plurality of untapped DNA chips,, can prevent that easy analysis is configured to technology that the base of each dna probe of array-like arranges above that and needs in the higher security management carrying out for each DNA chip.
Usually the diagnosis of in medical field, using is with in the DNA chip; What kind of genetic information dna probe for constituting it can detect; The user has clearly been indicated information; But from the social care that the source is provided that the base of this dna probe is arranged, sometimes from the information of clearly indication except this base arrangement itself.In addition, arrange, will produce the problem of keeping in security information such as imitation that the third party that do not obtain the usage license causes if can decipher the base of the dna probe of use.From these viewpoints, need prevent the technology deciphered, thereby also can't simply deciphering the base of the dna probe that constitutes the DNA chip, the third party arranges.
Summary of the invention
In order to solve above-mentioned problem; The object of the present invention is to provide: the special bonded probe of subject matter mass-energy is laid when making probe array on (location) given array-like point (spot) position on being arranged at the solid phase substrate material surface multiple; In each probe array, to laying the technology of change at random that (location) is not easy to discern at the Pareto diagram of the kind of the locational probe molecule of each rectangular point; According to having carried out point (spot) pattern that relevant change is handled, can change the placing device of the address, location (spot) of multiple probe; Corresponding therewith; For the multiple probe of laying according to the dot pattern that carries out relevant change processing; According to detected information on probe array; For each probe, on the basis of deciphering of having implemented the some position that this change handles, detect as the method for the multiple probe of purpose and for this reason and the proofing unit that uses.
The inventor is in order to solve said problem; When discovery is fixed the body material of a plurality of probes on being manufactured on the fixing base material; Even it is all when identical to be fixed on a plurality of probe kinds on the probe fixed substrate material that obtains; To each probe fixed substrate material, for example each make batch, respectively make body material, each makes day, each makes moon, each manufacturing installation, each manufacturing works, each mfr (manufacturer), each uses zone, each product modification, or moment arbitrarily, through changing the some position of fixing each probe; For the probe kind that is placed in each dot address, can realize encrypting.On the basis of relevant discovery; The placing machine that the inventor uses when proving the body material that can make on being manufactured on the fixing base material fixing a plurality of probes become on body material, lay a plurality of during to the special bonded probe of subject matter mass-energy; To each probe fixed substrate material; Can be according to the placing machine (spotter) of the position (pattern) of given information-change fitted with probes, thus the present invention accomplished.
Placing machine of the present invention (spotter); Be locational to a plurality of probe stationary of the special bonded of subject matter mass-energy at a plurality of points on the solid phase body material, in the manufacturing of probe fixed substrate material, use, on a position placing machine of fitted with probes, it is characterized in that: comprising:
Put the parts of each probe according to said a plurality of probes being distributed any, pattern Laian County, some position that constitute by a group dot address in the said a plurality of somes positions respectively; With the probe fixed substrate material that each is made, the some position pattern encryption unit of this position pattern being encrypted according to given information.
At this moment; Said some position pattern encryption unit has: stored energy is applicable to a plurality of somes position patterns of said probe fixed substrate material in advance; To each probe fixed substrate material of making, select one mechanism in the said a plurality of somes position patterns according to said given information; Function with some position pattern of this selection of probe fixed substrate material altering that each is made.Perhaps said some position pattern encryption unit has: to each probe fixed substrate material of making, as key, the reference point location pattern is carried out encrypt treatment to said given information, make the mechanism of the some position pattern that makes new advances; Have the probe fixed substrate material that each is made, change the function of this some position pattern that produces.
It should be noted that; In placing machine of the present invention (spotter); Said given information is the individual information of setting by each probe fixed substrate material of making, comprise the manufacturing lot number that uses in the identification of probe fixed substrate material of manufacturing at least, make numbering (manufacturing sequence number), date of built and time, manufacturing installation numbering, mfr (manufacturer), factory's identification number, make area number, territory of use's numbering, make revise numbering, any information or their combination or according to these information through analogizing or calculating and the information of unique derivation.
And in placing machine of the present invention; Corresponding with above-mentioned some position pattern change parts; Also hope to have: on said solid phase body material, or, put down in writing the parts of the pattern numbering of the said some position pattern of selecting in advance to being arranged on the framework on the said solid phase body material.Perhaps, also hope to have: on said solid phase body material, or to being arranged on the framework on the said solid phase body material, record is used to remove the parts of the key of said encrypt treatment.
And the parts of laying said each probe can adopt the mode of using ink-jet technology to give probe.
In addition, the present invention also provides the invention of the probe fixed substrate material of the placing machine manufacturing of using the invention described above.Be that probe fixed substrate material handle of the present invention is to a plurality of some positions of a plurality of probe stationary of the special bonded of subject matter mass-energy on the solid phase body material; It is characterized in that: use any one placing machine of the present invention, carry out said a plurality of probe laying on the solid phase body material with above-mentioned structure.For example, a plurality of probes that are fixed on the said solid phase body material are dna segments, and said probe fixed substrate material can have the shape of dna microarray.
In addition, the present invention also relates to have the function of the dot pattern of deciphering the encryption in the said probe fixed substrate material of the present invention, and can detect proofing unit based on the subject substances of a plurality of probes on the probe fixed substrate material.
Be that proofing unit of the present invention detects the said a plurality of probes in the locational probe fixed substrate material of a plurality of points of a plurality of probe stationary of the special bonded of subject matter mass-energy on the solid phase body material are placed in which position in the said a plurality of somes positions respectively; It is characterized in that: have:, decipher parts according to the some position pattern of given information encryption to becoming each probe fixed substrate material of detected object.At this moment; Use has said solid phase body material or is arranged on the placing machine of the invention described above of parts of pattern numbering that framework record on the said solid phase body material gives the some position pattern of said selection in advance, carries out said a plurality of probes in the said probe fixed substrate material to laying on the solid phase body material; Proofing unit is characterised in that: have: read said solid phase body material or be arranged on the parts of the said pattern numbering of the framework record on the said solid phase body material; According to the pattern that reads numbering and the group pattern numbering that gives a plurality of somes position patterns in advance respectively, the parts of the specific some position pattern that this probe fixed substrate material is selected.Perhaps; Use has said solid phase body material or is arranged on the placing machine of parts that framework record on the said solid phase body material is used to remove the key of said encrypt treatment, carries out said a plurality of probes in the said probe fixed substrate material to laying on the solid phase body material; Proofing unit is characterised in that: have: read the parts of removing this encrypted secret key; According to the releasing encrypted secret key that reads, through removing the encryption in the process that produces this new some position pattern, implement, the parts of the specific some position pattern that this probe fixed substrate made is gone out.
And; The present invention also is the invention of the dispenser that in dividing the step of annotating in the multiple-well plate that placing machine uses a plurality of probes in advance, uses; For example be when in the laying of each probe, using pin to lay method; Use the configuration corresponding, divide the invention of the dispenser that uses in the process of annotating the multiple-well plate that the pin placing device uses in advance a plurality of probes with dot pattern.Be that the present invention is the dispenser that branch is annotated a plurality of probes, at this moment, also provide to have and to divide the dispenser of the structure of the position pattern of annotating probe according to given information-change.
Be that dispenser of the present invention is using in the manufacturing to the locational probe fixed substrate material of a plurality of points of a plurality of probe stationary of the special bonded of subject matter mass-energy on the solid phase body material; The multiple-well plate that placing machine is used divides notes said a plurality of probes; It is characterized in that: have:, divide the parts of annotating each probe in the well of the correspondence on said multiple-well plate according to by the some position pattern that said a plurality of probes is distributed any one a group dot address in the said a plurality of somes positions constitute respectively; To each probe fixed substrate material of making, according to the some position pattern encryption unit of this position pattern of given information-change; According to said some position pattern of the probe fixed substrate material altering that each is made, distribute the parts of the well on the said multiple-well plate.It should be noted that this dispenser is as placing machine, be adapted at using when being placed to the pin placing device of a position to probe and use through the pin method of laying.At this moment; Said some position pattern encryption unit has a plurality of somes position patterns that stored energy in advance is applicable to said probe fixed substrate material; To each probe fixed substrate material of making; According to one mechanism in the said a plurality of somes position patterns of given Information Selection, has the function of the some position pattern of this selection of probe fixed substrate material altering that each is made.Perhaps; Said some position pattern encryption unit has the probe fixed substrate material that each is made; With given information is key; Encrypt the reference point location pattern, make the mechanism of the some position pattern that makes new advances, have the function of this some position pattern that produces of probe fixed substrate material altering that each is made.
It should be noted that; Said given information is the discrete information that each probe fixed substrate material of making is set, comprise the manufacturing lot number that uses in the identification of probe fixed substrate material of manufacturing at least, make numbering (manufacturing sequence number), date of built and time, manufacturing installation numbering, mfr (manufacturer), factory's identification number, make area number, territory of use's numbering, make revise numbering, any information or their combination or according to these information through analogizing or calculating and the information of unique derivation.
Simultaneously, the present invention also is provided in said placing machine of the present invention or the dispenser, lays or divides the program of using in the operation of the position pattern of annotating probe according to given information-change.
Stipulate that promptly the program of the change action of of the present invention some position pattern can be carried out by computingmachine; Using to a plurality of somes positions on the solid phase body material of a plurality of probe stationary of the special bonded of subject matter mass-energy the time; It is characterized in that: is the information definition that is made up of any one a group dot address of said a plurality of probes being distributed said a plurality of somes positions respectively a position pattern, and this program comprises: import the operation of given information; The operation of some position pattern according to the specific correspondence of given information of input; Export the operation of specific corresponding points position pattern.At this moment, can comprise according to the corresponding operation of the given Information Selection of said input: one that from a plurality of somes position patterns of the probe fixed substrate material that can be applicable to manufacturing of storage in advance, selects specific be the step of the some position pattern of said correspondence.Perhaps; Operation according to the some position pattern of the specific correspondence of given information of the said input of stipulating in the said program can comprise: through with said given information as key; The reference point location pattern is carried out encrypt treatment, and the some position pattern that new system is produced is specific to be the step of the some position pattern of said correspondence.
In addition; Regulation of the present invention divides the program of the change action of annotating the position pattern to be carried out by computingmachine; Using to a plurality of somes positions on the solid phase body material of a plurality of probe stationary of the special bonded of subject matter mass-energy the time; It is characterized in that: is the information definition that is made up of any one a group dot address of said a plurality of probes being distributed said a plurality of somes positions respectively a position pattern; According to said some position pattern, be defined as branch to the positional information that makes each probe group wells corresponding and annotate the position pattern with each well on the multiple-well plate that placing machine is used, this program comprises at least: import the operation of given information; According to the given information of input, the operation of the some position pattern of specific correspondence; Through the conversion of carrying out annotating the position pattern from the some position pattern of specific correspondence to this minute, the branch of specific correspondence is annotated the operation of position pattern; Export the operation of the branch notes position pattern of specific correspondence.It should be noted that this placing machine is based on the placing device that pin is laid method.At this moment; According to the given information of said input, the operation of the some position pattern of specific correspondence can comprise: the step of one that from a plurality of somes position patterns of the probe fixed substrate material that can be applied to make of storage in advance, selects specific some position pattern for said correspondence.Perhaps; Given information according to said input; The operation of the some position pattern of specific correspondence can comprise: through with said given information as key, the reference point location pattern is carried out encrypt treatment, the step of the specific some position pattern for said correspondence of the some position pattern that new system is produced.
It should be noted that; In above-mentioned program of the present invention; Said given information is the discrete information that each probe fixed substrate material of making is set, comprise the manufacturing lot number that uses in the identification of probe fixed substrate material of manufacturing at least, make numbering (manufacturing sequence number), date of built and time, manufacturing installation numbering, mfr (manufacturer), factory's identification number, make area number, territory of use's numbering, make revise numbering, any information or their combination or according to these information through analogizing or calculating and the information of unique derivation.
The present invention also is provided in the above-mentioned proofing unit of the present invention, and for each probe that is placed on the probe fixed substrate material, regulation is deciphered the invention of program of operation of the dot pattern of encryption.The program that is the operation of the present invention's dot pattern of stipulating to decipher encryption can be carried out on computers; Which in detecting, use the device that the said a plurality of probes in the probe fixed substrate material of a plurality of probe stationary of the special bonded of subject matter mass-energy on the surface of solid phase carrier or body material is placed in the position in the said a plurality of somes positions respectively; It is characterized in that: the information definition that constitutes a group dot address of the some position of being laid a plurality of probes by expression is a position pattern; Have the detection information that obtains according to from this probe fixed substrate material, decipher the function of each the probe fixed substrate material that becomes detected object being carried out the some position pattern of encrypt treatment according to given information; This program comprises: the operation of the detection information that input obtains from said probe fixed substrate material; Take out the operation of the partial information of the some position pattern be used to decipher said probe fixed substrate material from the detection information of input; According to the said partial information of taking out, decipher the operation of the some position pattern of this probe fixed substrate material; Export the operation of the said some position pattern of deciphering.In deciphering the program of usefulness; Use has on the said solid phase body material or to being arranged on the placing machine of the present invention of parts of pattern numbering that framework record on the said solid phase body material gives the some position pattern of said selection in advance; Carry out a plurality of probes laying on the solid phase body material described in the said probe fixed substrate material; The partial information that is used to decipher the some position pattern on the said probe fixed substrate material is the pattern numbering of this record; According to the said partial information of taking out; The operation of deciphering the some position pattern of this probe fixed substrate material can comprise: according to the pattern of said record numbering, give the pattern numbering of a plurality of somes position patterns respectively in advance, the specific step of numbering for the pattern of deciphering of the some position pattern of the pattern numbering that gives this record.In addition; In the program of deciphering usefulness of the present invention; Use has on the said solid phase body material or to being arranged on the framework on the said solid phase body material; The placing machine of the present invention of the parts of this encrypted secret key is removed in record to said encrypt treatment; Carry out a plurality of probes laying on the solid phase body material described in the said probe fixed substrate material; The partial information that is used to decipher the some position pattern of said probe fixed substrate material is on the said solid phase body material or to being arranged on the said encrypted secret key of releasing of the framework record on the said solid phase body material, according to the said partial information of taking out, the operation of deciphering the some position pattern of this probe fixed substrate material can comprise: according to removing said encrypted secret key; Remove the encryption of said enforcement, the specific step of the some position pattern that this probe fixed substrate made is gone out for the some position pattern deciphered.
The present invention is for above-mentioned program of the present invention; Form to record and narrate the computer-readable recording medium of this program with the manifestation of calculating the function execution provides; The computer-readable recording medium of promptly storing program of the present invention is at least one program that storage is recorded and narrated with the manifestation of calculating the function execution on computer-readable recording medium, and it is characterized in that: at least one of said program is to have any one program of the present invention of said structure.
Finally; The present invention provides the probe fixed substrate material of combination the invention described above and the genetic diagnositc system of proofing unit; Be that genetic diagnositc system of the present invention uses handle to the probe fixed substrate material of a plurality of probe stationary of the special bonded of subject matter mass-energy on the surface of solid phase carrier or body material; The subject substances that comprises in the sample with the special bonded probe of this subject matter mass-energy on the said probe fixed substrate material is combined; Carry out the detection of bonded subject substances; Wherein: the said probe fixed substrate material of use is any one the probe fixed substrate material of the present invention that has in the said structure, has in the detection of said bonded subject substances, uses the system architecture of any one proofing unit of the present invention in the said structure.
And; In order in described the present invention, to use; The present invention also is provided at the recording medium of the multiple some position pattern that record is made in advance on the recording medium; Be the multiple some position pattern that one of recording medium of the present invention records the placing machine that is used for the invention described above; Wherein: the some position pattern encryption unit of said placing machine has: stored energy is applicable to a plurality of somes position patterns of said probe fixed substrate material in advance, to each probe fixed substrate material of making, from said multiple some position pattern, selects one mechanism according to given information; Function with some position pattern of this selection of probe fixed substrate material altering that each is made.
In addition; One of recording medium of the present invention records multiple some position pattern of the dispenser that is used for the invention described above; Wherein: the some position pattern encryption unit in the said dispenser has: stored energy is applicable to a plurality of somes position patterns of said probe fixed substrate material in advance; To each probe fixed substrate material of making, from said multiple some position pattern, select one mechanism according to given information; Function with some position pattern of this selection of probe fixed substrate material altering that each is made.
In addition; One of recording medium of the present invention records a plurality of somes position patterns of the proofing unit that is used for the invention described above; Wherein: said proofing unit uses said placing machine to become a plurality of probes laying on the solid phase body material described in the said probe fixed substrate material of subtend, has: read on the solid phase body material of this probe fixed substrate material or to the parts of the said pattern numbering that is arranged on the framework record on this solid phase body material; Storage give respectively in advance said a plurality of somes position patterns pattern numbering, with each self-corresponding a group dot address, according to reading to obtain the pattern numbering, the parts of the specific some position pattern that this probe fixed substrate material is selected.
According to the present invention; For a plurality of probes of fixed on the probe fixed substrate material; The encryption of some position of carrying out the change of dot address becomes easy; So diagnose with the DNA chip as gene; The combination that remains in the subject substances on the DNA chip after the use itself is equivalent to each patient's personal information as a result, even the third party observes the DNA chip after the relevant use, the result who encrypts the probe stationary order is the danger that can reduce simply to be deciphered from this DNA chip of finishing using by the third party diagnostic result.
The a plurality of probes itself that use in the making of the probe fixed substrate material that uses in the medical field are for example for each dna probe on the DNA chip; Spell out information for the subject substances of detected object; But from the social care that the source is provided that the base of dna probe is arranged, sometimes from the information that spells out except the base arrangement of each DNA chip itself.In addition, arrange, will produce the problem of keeping of security informations such as the third party who does not obtain the usage license imitates if can decipher the base of the dna probe of use.From these viewpoints, the application of the invention, the third party can't decipher the base of the dna probe that constitutes the DNA chip simply and arrange, and helping very much to prevent with the imitation is deciphering of purpose.
Describe with the accompanying drawing bonded from following, other characteristics of the present invention and advantage will become obviously, and in the accompanying drawings, similar reference marks indicates same or analogous part.
Description of drawings
Following brief description accompanying drawing.
Accompanying drawing constitutes the part of this specification sheets, is used to describe embodiments of the invention, and principle of the present invention is described.
Fig. 1 is that placing machine of the present invention is represented when the dot address of each probe of dispense probes fixing base material in pattern ground, selection mode one example and the figure that is equivalent to the data flow diagram of this selection operation of the some position pattern of the alter operation of some position pattern.
Fig. 2 is the figure that an example of the dot pattern when laying 16 kinds of probes to the microarray shape is described.
Fig. 3 is that the algorithm that generates randomized number is used in expression, generates the figure of algorithm one example of the dot pattern when laying to the microarray shape to 16 kinds of probes.
Fig. 4 is the Pareto diagram of the probe kind (probe numbering) of each dot address of distributing to the microarray shape in the dot pattern of representing to generate.
Fig. 5 be pattern ground expression according to the detected result to the probe fixed substrate material of proofing unit of the present invention, the information of dot pattern numbering, carry out the probe fixed substrate material each probe dot address differentiation, to the operation associated example of the detected result of each probe, be equivalent to the figure of the data flow diagram of this operation.
Embodiment
Below, describe embodiments of the invention in detail in conjunction with accompanying drawing.
Below, further explain the present invention.
When placing machine of the present invention is fixed the body material of a plurality of probes on being manufactured on the fixing base material; Even it is all when identical to be fixed on a plurality of probe kinds on the probe fixed substrate material that obtains; In each probe fixed substrate material itself; According to its make in batches, respectively make body material, each makes day, each makes moon, each manufacturing installation, each manufacturing works, each mfr (manufacturer), each uses zone, each product modification, perhaps moment arbitrarily; Through changing the some position of fixing each probe,, can realize encrypting for the probe kind that is placed in each dot address.
The present invention lays a plurality of probes in the probe fixed substrate material as object, and fixed solid phase body material is suitably to select according to the use of the probe fixed substrate material of making, and does not limit solid phase body material itself especially.For example the solid phase body material is array-like for laying a plurality of probes; And during fixed microarray type; If service condition that the subject substances of the probe of the relevant microarray shape of consideration use detects and high versatility, the solid phase body material that just suitable use shows dull and stereotyped surface is glass substrate or plastic.In glass substrate, the non-alkali glass substrate of alkali-free composition or quartz substrate are examples of the body material of more hoping in substrate material itself.In addition, for these solid phase body materials,, carry out in the immobilized process employable process for fixation and reported multiple at the various probes of its surface mount.
As the method for stationary probe on body material, each kind according to probe proposes the whole bag of tricks, uses according to purpose.For example, well-known have: dna probe is used solid-phase synthesis, and the dna molecular of arranging through the base that on body material, has purpose synthetic made the method that is fixed on the dna probe on the body material; On body material, give the DNA of making in addition, make DNA be attached on the body material and fixed method.It should be noted that, giving laying in the operation on the body material DNA that makes in addition, use the skill of handling needles or methods such as impact molding or ink jet method.
Synthetic method as the dna probe that on body material, is configured to array-like; Well-known have: for example described in No. 51438545 specification sheets of USP; The zone of the selection from the solid phase synthesis body material; Remove the protection base of 5 ' end through acvator; Make monomer act on the zone of said selection,, on body material, synthesize the method that has the monomer of arranging as the base of purpose (dna molecular) respectively through repeating and 5 ' terminal bonded operation with the protection base that can remove.
Placing machine of the present invention adopts usually and is placed in substrate material surface to the probe of making in addition; Immobilized mode; But also comprise: adopt and use above-mentioned solid-phase synthesis; The probe of synthetic purpose on body material as the mode that is fixed at the probe of this dot address (position), is realized the device of the state of laying of equal value.
In addition; After being placed in pre-prepd probe on the body material; Be fixed on the lip-deep method of body material, well-known have: it is said for example to open flat 8-23975 communique like the spy, makes body material itself with the macromolecular compound with carbon imide base; Or on body material, bear the material layer of the fixedly usefulness that constitutes by macromolecular compound with carbon imide base; Make to have to contact the macromolecular compound that is present in substrate material surface with carbon imide base with reactive active substance biologically of this carbon imide base, through with the reaction of this carbon imide base, carry out the fixed method of covalent linkage property.In addition, well-known have: it is said to open flat 8-334509 communique like the spy, in the detection of biological active substance; Use is through on the compound with carbon imide; Carry out formation, carry out fixed method, the method that detects through the covalent linkage of this carbon imide base.
And; Open in the 2001-178442 communique the spy; Put down in writing following method: the portion endways that enables to use the mercaptan modifier to import with liquid phase has thiol group (dna segment SH); And have can with this thiol group (SH) reaction and the reactive substituent chain molecule that forms covalent linkage are fixed on lip-deep solid phase carrier at other the different ends of the end of the chain with said reactive sub stituent place and contacts, in view of the above, through thiol group (SH) and the substituent reaction of this reactivity; Between dna segment and chain molecule, form covalent linkage, be fixed to dna segment on the surface of solid phase carriers.In addition; Change and record: as can with thiol group (SH) reaction and form the reactive substituent example of covalent linkage, can use from by Malaysia imines two Yi Luji, α, beta-unsaturated carbonyl (＞C=C=O), α-halogen carbonyl (COX), halogenation alkyl ((C nH 2n)-X), Soluol XC 100-2-Yi Luji, the disulfide group (sub stituent that comprises reactive functional groups that the mass selection that S-S-) constitutes is selected.
For as stated the fixed method that is placed in the various probes on the body material, just to the fixing means of dna segment, just a lot of at least methods.It should be noted that, in the present invention, for the probe kind of laying or its fixing means, mechanism, restriction especially.
In addition; As the method that is placed in probe on the body material; Can enumerate out the method that gives substrate material surface the aqueous solution of dissolving in the water-based medium or dispersion probe; For example open the ink jet method described in the flat 11-187900 communique or the skill of handling needles or pin and around-France etc., be placed in substrate material surface with base property base through the spy.
For the setting method of the aqueous solution that uses probe, in above-mentioned various setting methods, particularly ink jet method can be placed to correct position with high-density, so be to be applicable to setting method of the present invention.When the substrate material surface of laying is electrode etc., compare based on the skill of handling needles that contacts of pin with using, if use the ink jet method of laying, just have the advantage of the damage that the mechanical contact on the surface that counter electrode etc. can not take place causes with noncontact.In installation based on ink jet method; The liquid that comprises probe is injected in use in superfine nozzle, near the top of this nozzle in the moment heating, from the top of nozzle the drop that comprises probe of minimum capacity is flown out; Circle in the air in the space, be attached to the step of substrate material surface.At this moment, the drop amount that sprays from nozzle is a denier, but this measurer has the advantage of the high reproducibility of performance.In setting method based on the ink jet method that correctly is controlled to be the drop amount of ejection denier; If when constituting the medium composition of the liquid comprise probe and be from ink gun ejection drop; The probe of medium is not impacted in fact; And be to satisfy the medium that use ink gun normally to spray to form, just for not limiting especially.The ink gun that for example uses is when giving heat to medium and making the foam ink gun of mechanism of its ejection, and the water-based medium of hoping to comprise USP Kosher, sulfo-glycol ether, Virahol, acetylene alcohol are as comprising the medium composition that comprises in the liquid of probe.For example, when probe was dna segment, suitable use comprised the water-based medium of USP Kosher 5～10 quality %, sulfo-glycol ether 5～10 quality %, acetylene alcohol 0.5～1 quality %.In addition, when the ink gun of use was to use piezoelectric element to make the piezoelectric ink jet head of liquid ejection, the water-based medium of hoping to comprise terepthaloyl moietie, Virahol were as comprising the medium composition that comprises in the liquid of probe.For example, when probe was dna segment, suitable use comprised the water-based medium of terepthaloyl moietie 5～10 quality %, Virahol 0.5～2 quality %.
Spray the liquid that comprises probe that uses the water-based media production with described medium composition from ink gun, when being attached on the body material, the shape of drip point becomes circle, and the point range of the drop that adheres in addition can not be accompanied by the infiltration of water-based medium and enlarge.When laying the drop that comprises probe with high-density, also can suppress between adjacent point, the water-based medium ooze out each other, some banded phenomenon.If the use ink jet method, being placed in which locational dot address control to which probe can easily change with program, so in the present invention of the dot address that is necessary to change each probe, be the suitable method of laying.It should be noted that in the present invention, the composition that comprises the water-based medium that use in the making that offers liquid a little is not limited to the above composition of enumerating.
The probe fixed substrate material uses and to be fixed on a plurality of probes on the body material, the detection of a plurality of subject substances that can implement simultaneously to comprise in the sample or quantitatively.Because these advantages, DNA chip are suitable for the analysis that multiple gene are found or a base is polymorphic etc., have at least in the purposes of the research field of using these gene to analyze and the two big use fields such as purposes of the medical field that carries out the gene diagnosis.At this moment; When in the purposes of gene diagnosis, using the DNA chip; The DNA chip that uses in each patient's the diagnosis is represented genetic diagnostic result; If distinguish the name that has position and the patient who uses this DNA chip of the probe that is fixed on the DNA chip, even then the third party can judge that also the personal information of reading this patient is a diagnostic result.At this moment; Even the DNA chip that the multiple probe of fixed is identical; Through changing the some position (pattern) of each probe; Make the third party be difficult for the processing that has the position of the probe of particular fixed on the DNA chip,, also can reduce the danger of the diagnostic result of analyzing each patient without authorization significantly even the third party obtains patient's name, the DNA chip of finishing using.
One example of the method for the some position (pattern) of each probe of change that uses in the placing machine of the present invention has for each probe fixed substrate material; For example according to process shown in Figure 1; The multiple dot pattern 203 that preparation generates according to product information (detecting probe information) 201 in advance; According to making numbering (sequence number) 202, implement a kind of method of selection 204 of dot pattern from the multiple dot pattern (dot pattern collection) 203 that generates in advance.According to being respectively a kind of dot pattern 204 that each probe fixed substrate material is selected, generate the placing machine control command 205 of control, the action 206 of change placing machine based on the configuration that is placed in the probe on each dot address of placing machine at every turn.For example when the probe fixed substrate material be to be placed in 16 kinds of probes when being configured in the 16 rectangular dot addresses; As shown in Figure 2; According to this product information (detecting probe information), from a plurality of dot patterns that generate in advance, the set of for example selecting 10 kinds of dot patterns is as dot pattern collection 203.It should be noted that each probe that 101 expressions are laid.For each probe fixed substrate material, make numbering (sequence number) 202 numerical value to it and turn to natural number, and according to making numbering (sequence number) variation point pattern; When the numeral of next bit is 1; For the pattern of pattern numbering 1, when the numeral of next bit is 2, be the pattern of pattern numbering 2.
It should be noted that in each dot pattern shown in Figure 2, the numeral shown in each dot address is the numbering (below be called probe numbering) of the kind of 16 kinds of probes of expression.In dot pattern arbitrarily, with the identical probe kind of probe representative of each probe numbering expression, at this moment, which probe kinds of information is this a group each probe numbering of common on the probe fixed substrate material be equivalent to is equivalent to product information (detecting probe information).In addition, in 16 dot addresses the sum of method (dot pattern) of 16 kinds of probes of configuration exist 16! Individual, but from wherein, as pattern numbering 1～10, the sum of the method for selecting 10 dot patterns in order becomes very large number, for (16! ) (16!-1) ... (16!-9) (16!-10) individual.In other words, the possibility that the selection of the dot pattern collection of pattern numbering 1～10 shown in Figure 2 itself can be carried out identical selection is extremely low, becomes the state of encryption.Therefore, for each probe fixed substrate material,, also become the state of highly encrypting even adopt the easy selection reference of selecting the pattern numbering identical with the next bit numerical value of each manufacturing numbering (sequence number) 202.
And, making numbering (sequence number) according to this, among the dot pattern collection, select the operation of a pattern numbering, if adopt more complicated selection operation, then become the state of more highly encrypting.For example; Change to n to the pattern kind that constitutes the dot pattern collection; Be transformed to the manufacturing numbering (sequence number) of the natural number of said 10 systems record the record of n system; And through adopting the selection reference of selecting the pattern numbering identical with the next bit numeral, the third party can't infer the fact that comprises the map function from 10 systems to the n system, so become the state of more highly encrypting.Perhaps; Numerical value to the manufacturing numbering (sequence number) of the natural number of 10 systems record calculates processing arbitrarily; For example,, adopt the selection reference of selecting the pattern numbering identical with the next bit numeral with the record of n system for the value that obtains each bit digital addition; The fact that then comprises multistage numerical value processing operation is that the third party can't infer, so become the state of more highly encrypting.
In above-mentioned explanation, for the purpose of simplifying the description, use probe species number and the identical example of point (dot address number).But in fact, the probe species number of the dot pattern of preparing for encryption need not be consistent with the actual necessary number of probes of product; In addition; With the necessary number of probes of the product of reality coupling, to take time and energy the load that becomes of the management of dot pattern sometimes when preparing corresponding dot pattern.For example counting (dot address number) also after a little while when probe species number ratio, can be in each dot pattern, is placed to actual probe kind of laying in the dot address that is assigned the probe numbering state of vacating remaining dot address.For example, be 16 kinds of dot patterns that probe is used in example shown in Figure 2, but when the probe that reality is used is 10 kinds, have on the dot address that is placed to probe numbering 1～10 usefulness, and be numbered the method for not laying on the dot address of 11～16 usefulness at probe.
The address of the state of not laying whatever of vacating replace to be set, also to consider the situation of laying a plurality of illusory probes or identical probe.If use example just now to specify; Then be in the dot address of probe numbering 11～16 usefulness of not laying whatever, the probe that does not have the detected object with product direct relation has been placed in the method for the probe of other positions (address) as illusory probe or repetition fitted with probes numbering 1,2 etc.At this moment, compare during with simple encryption, deciphering of the third party becomes difficult more.
And; In the example of Fig. 2, the dot address of laying each probe is the matrix shape that is configured on the square, but is not limited to this matrix shape; Can be counting and horizontal count different rectangles, Polygons of indulging; Also can be in order to improve density a little, be configured to the reticulation (cellular) of fine and closely woven filling, the not shape of special restriction matrix to point.
In addition,, can mix 2 kinds of probes, lay a dot address when probe species number n counts m also for a long time than dot address.
And as stated; During according to the given Information Selection dot pattern of the characteristic of each probe fixed substrate material; The given information of using is except making numbering (sequence number); For example can be to be date of built and time change the numerical value of sequence, as the method for using in the given information of each probe fixed substrate storeroom change.Certainly, also can be the random value that gives each probe fixed substrate material, can be to comprise the numerical value of making lot number, manufacturing installation numbering, manufacturing area number, territory of use's numbering, product modification numbering etc.It should be noted that, in the present invention, according to the operation of the given Information Selection dot pattern of the characteristic of each probe fixed substrate material be not limited to above-mentioned for example.
In addition, need not always be built in the dot pattern collection in the placing machine, the device of ability input point pattern set can be set, in good time the input point pattern set in placing machine.Particularly, also can be that the floppy disk reading device is set in placing machine, be recorded in the method for the dot pattern collection on the floppy disk in advance from said reading device input.
Carry out each probe fixed substrate material that forms a little and use by placing machine of the present invention; When estimating with the having or not of the special bonded subject substances of each probe; The party who uses hopes that this can easyly be identified in the probe fixed substrate material of use, disposes the probe of which probe numbering at the each point address line when detecting.If the consideration this point just hopes that in each probe fixed substrate material, the information of which dot pattern has been used in record on the zone beyond the probe stationary position in microarray, the framework that the probe fixed substrate material is used etc.Record considers to have 2 d code, barcode, colour coding etc. for the method for the information of the dot pattern that uses etc., but is not limited to these codes record methods.For example; When the result's of each probe fixed substrate material detection, when using the method with the observation of fluorescent scanning appearance, if use fluorescent substance; Describe 2 d code in the zone of the not stationary probe in microarray; Detect mode with the fluorescent scanning appearance, just do not need new test set, so hope it is this method based on the fluorescence of this 2 d code.
It should be noted that; Be not only the framework of narrow sense at this said framework; For example be used for from the protecting materials of pollution substance or surge protection probe fixed substrate material physically or structure supporter, also comprise and mean the appendicular generalized framework that can provide with probe fixed substrate material one as the encapsulation of product or files such as bale packing materials, working instructions, other carrier etc.
In addition, during according to the given Information Selection dot pattern of the characteristic of described each probe fixed substrate material, replace the method selected from the dot pattern collection that specific in advance dot pattern constitutes, also can adopt the method that at every turn generates dot pattern according to given information.For example, when in 16 dot addresses, laying 16 kinds of probes, according to the algorithm of generation Pareto diagram shown in Figure 3; For example make numbering (sequence number) according to given information; The randomized number A (1) that generation is arranged probe numbering again, A (2) ... A (16), as shown in Figure 4, according to this random number series; Number the arranged of distributing to 16 dot addresses to probe, can generate a dot pattern.Probe numbering on the point that 102 expressions of Fig. 4 are encrypted.Be in the algorithm shown in Figure 3, in the generation step of simulation random number series, adopt the value of for example making the seed of numbering (sequence number) unique selection according to given information, generate a series of simulation random number series.To each probe fixed substrate material; According to given information for example make numbering (sequence number) and if the value of the seed of unique selection is for example selected the identical value of next bit numeral with the manufacturing numbering (sequence number) of the natural number of said 10 systems record, just generate 10 kinds of different respectively dot patterns.
In the present invention, random number series means ordered series of numbers x 1, x 2, x 3To be arranged in be irregular in appearance, x arbitrarily kBecome x kThe possibility of＜C only exists with ... C, does not exist with ... x K-1Especially in the present invention, use ordered series of numbers x usually 1, x 2, x 3Constitute by natural number.
Exist in the randomized number: the natural numerical value of certain scope of skew is not with the randomized number that equally distributes of isoprobability appearance; Probability of occurrence is not an isoprobability, the randomized number of various probability distribution such as the distribution of X side, γ distribution, triangle distribution, normal distribution, logarithm distribute, the distribution of ripple pine.
When in computingmachine etc., using random number series, the general simulation randomized number that generates according to given algorithm of using.In addition, in the algorithm of the simulation randomized number that employable generation equally distributes in computingmachine, know the serial randomized number of randomized number genetic method, M that linear contract law (103), Knuth are arranged, a lot of methods such as randomized number genetic method of Wichmann-Hill.It should be noted that, in the present invention, when using the simulation randomized number that equally distributes, the not special algorithm that limits the simulation randomized number of using that equally distributes.
The majority of the algorithm of simulating randomized number from the generation of knowing in the past,, then generate different simulation random number serieses according to this seed if consider to be called the numeral that becoming of seed is used to generate the basis of simulating random number series.It should be noted that, because be the algorithm that the value of each seed is generated a simulation random number series respectively, so, if distinguish the value of each seed of use, just can generate identical simulation random number series once again.If use this characteristic, when detecting, can confirm originally lay the generation of the dot pattern in the step time simulation randomized number generating algorithm used kind and the value of this seed, just can generate the dot pattern of selecting in this probe fixed substrate material once again.Promptly when detecting, can distinguish each probe of this probe fixed substrate material with which dot pattern is laid.
Choosing in advance then originally lay the generation of the dot pattern in the step time simulation randomized number generating algorithm used; And the value of seed can use the manufacturing numbering of this probe fixed substrate material or date of built and the time change natural value as sequence, uses the mode of this value; Perhaps replace making numbering or date of built and time, use manufacturing installation numbering etc.If this probe fixed substrate material institute inherent value then can be the value of setting at random.It should be noted that; When detecting; If use the value of the seed of this probe fixed substrate material use; Carry out the differentiation of dot pattern, then when this probe fixed substrate material is microarray, hope probe Guan County in this microarray beyond placing the zone or be arranged on that record on the framework on the probe fixed substrate material etc. is deciphered key as encryption and the value of the seed that uses.For example, as probe result, when adopting the detection mode of observing with the fluorescent scanning appearance for use probe fixed substrate material; Use fluorescent substance; Is the information conversion that comprises seed 2 d code, draws in the position of the not stationary probe in microarray, through detecting this fluorescence with the fluorescent scanning appearance; On probe result's basis, become the form of the information that can read 2 d code.The form of using fluorescent substance to put down in writing the information of the value that comprises this seed does not need new test set, so be one of method of hoping.
The algorithm of the algorithm of the generation dot pattern that uses in the placing machine of the present invention, generation simulation randomized number is not limited to above-mentioned example; In addition; Decipher the description method of key as encryption, enumerated 2 d code, barcode, colour coding etc., but be not limited to these methods.
The function that changes this dot pattern need not be built in the manufacturing installation of the body material with a plurality of probes; Also consider and for example generate several dot patterns in advance on computers; Data are recorded and narrated in the action that is transformed to manufacturing installation, carve at a time to change it, in fact the variation point method of patterning.
As stated, in placing machine of the present invention, when the riding position on the change probe fixed substrate material, suitable employing has the ink-jetting style of the advantage that can carry out this position change easily.In addition, when in laying, using the skill of handling needles, in general, in the well plate, get the top of each pin to the liquid dispensing that comprises probe, be placed to the position of correspondence minute annotating liquid in each well.Compare with ink-jetting style, when the skill of handling needles, the position that can lay or order are specific by the configuration of the pin that uses.Therefore, can be employed in when the well plate divides notes, divide the kind of annotating the probe in each well promptly to divide the notes pattern through change, change is placed to the kind of the probe in each dot address, the mode of variation point pattern in fact.
In addition; The use of well plate is not limited to the skill of handling needles; In ink jet method; Consider that employing for example when multiple medium that comprise probe are injected in the ink-jet that can lay the multiple medium that comprise probe simultaneously in head, divides these medium that comprise probe in advance and annotates on the well plate, a step of supplying with head to ink-jet from the well plate.At this moment, also exist to make the device and the program that drive ink gun certain, when this well plate is carried out the branch notes, annotate pattern through the change branch and come the variation point method of patterning.
The detected result to subject substances of the probe fixed substrate material of making through the placing machine that uses the invention described above, for example in the DNA chip, with the hybrid reaction of the subject substances of having implemented sign in advance after, use the sign of implementing to detect.At this moment, according to how subject substances being identified, the detection method of use is different.For example, when being to use the fluorescence labelling of fluorescent substances such as rhodamine when sign, fluorescent scanning appearance or the fluorescent microscope that can observe this fluorescence labelling are arranged.It should be noted that, the identification method of subject substances or the detection method of correspondence are not limited to cited fluorescence labelling.
And in detection, though distinguish the special bonded dot address that realizes with which subject substances,,, then can't explain the detected results such as association reaction that produce which probe and subject substances if can't discern the kind that is configured in the probe in this dot address.Therefore,, be necessary to confirm that the probe kind that is configured in each dot address is a dot pattern in the probe fixed substrate material that uses, be necessary to explain the reaction of which probe and subject substances with the detection while.
For example,, detect these information simultaneously, can decipher corresponding dot pattern when the seed of the pattern randomized number of using in the generation that on the probe fixed substrate material, records dot pattern numbering or dot pattern, when deciphering information such as key.And ought be not on the probe fixed substrate material; Be arranged on the framework on the probe fixed substrate material or in the encapsulation of holding the probe fixed substrate material in the notion that is included in framework at this etc., recording the dot pattern numbering or decipher information such as key; And can't detect simultaneously the time; Be necessary to read in addition, to deciphering these information of device input.
Number or decipher the method for information such as key as other input point pattern; Be attached to the keyboard input of deciphering device except use; Consider the code reader that barcode or 2 d code, colour coding etc. are set in addition, the method that reads and import, but be not limited to the method that these are enumerated.It should be noted that, can be after detection of end operation, independent enforcement deciphered processing, therefore, can select to separate with proofing unit that the form of deciphering device, any form that is built in the form in the device being set.
On the probe fixed substrate material seed of the above-mentioned dot pattern of record numbering, simulation randomized number, decipher information such as key; With the detection of probe bonded subject substances in, use identical detection method, when reading; Read it; Through being built in the mechanism that deciphers in the proofing unit, can in detecting operation, decipher.
When in sign, using fluorescent substance to subject substances; When detecting fluorescence; If use fluorescent substance record dot pattern numbering, simulation randomized number in the zone of stationary probe not seed, decipher information such as key, just do not need new test set, so hope it is this method.
Example as the apparatus structure of proofing unit of the present invention; Fig. 5 is illustrated in the sign to subject substances and uses fluorescent substance; In addition, also can use fluorescent substance to be logged into the apparatus structure example that can be applied to the probe fixed substrate material on the probe fixed substrate material to the information of dot pattern numbering.When the probe fixed substrate material is the form of DNA chip; After sample carried out hybrid reaction; In advance to subject substances with fluorescent substance as sign, the test set of using with fluorescence observation 302 is observed through hybrid reaction, forms the having or not and measure of subject substances of special mixtinite with probe.With the detecting operation 301 of this mixing resultant, also observe the record position that records the dot pattern numbering on the probe fixed substrate material with fluorescent substance through test set 302.As a result, in the detecting operation 301 of mixing resultant, obtain in which dot address, observing the existence of fluorescence labelling, perhaps obtain the mensuration result of amount as mixing resultant 307.Be logged into the record position that the dot pattern on the probe fixed substrate material is numbered through seeing side with fluorescent substance,, read the detection 303 of dot pattern numbering, as 304 inputs of dot pattern numbering as information encoded.
Carry out the dot pattern collection of laying the probe configuration in the dot address of using the operation corresponding from being illustrated in, select to distribute to the dot pattern that reads and number 304 dot pattern, the analysis operation 306 of specified point address with each dot pattern numbering.Carry out from the probe of analyzing of laying each probe numbering dot address 308, with the mixing resultant 307 of each point address detected, represent that the probe of each probe numbering carries out and the special bonded product information of what kind of subject substances (detecting probe information) 311, extract out the sample that is used for measuring comprise which subject substances, perhaps for the diagnostic operation 309 of the information of content.The diagnostic message of extracting out can intactly be exported, and in addition, adds the explanation corresponding with this diagnostic message, can be as diagnostic result 310 outputs.
It should be noted that dot pattern collection 305 need not be built in the proofing unit in advance, the device of ability input point pattern set for example can be set, in good time the input point pattern set in proofing unit.Particularly, also can be that the floppy disk reading device is set in proofing unit, be recorded in the method for the dot pattern collection on the floppy disk in advance from said reading device input.
In addition; When not being the method for selecting from said dot pattern collection; And adopt when generating the mode of dot pattern according to given information at every turn; Decipher the kind of the simulation randomized number generating algorithm of using in the device or the value of its seed with input or automatic the detection,, make same dot pattern according to the making method of above-mentioned dot pattern.As stated; If the kind of specific analog randomized number generating algorithm and the value of seed; Just can generate and the identical pattern of making by placing machine of dot pattern; So use it, carry out carrying out special bonded product information (detecting probe information) from the mixing resultant that detects by proofing unit, probe and what kind of subject substances of representing each probe numbering, extract out the sample that is used for measuring comprise which subject substances, perhaps for the diagnostic operation of the information of content.The diagnostic message of this extraction can intactly be exported, and in addition, adds the explanation corresponding with this diagnostic message, can export as diagnostic result.It should be noted that this is deciphered device and also can be included in proofing unit etc.
Therefore; The present invention is not limited to embodiment described above, for a person skilled in the art, can carry out various distortion and modification to the foregoing description at an easy rate; But these distortion and only revise otherwise break away from spirit of the present invention and aim just all should belong to protection scope of the present invention.

Claims (3)

1. proofing unit; Detect the said a plurality of probes in the probe fixed substrate material that forms on a plurality of somes positions of a plurality of probe stationary of the special bonded of subject matter mass-energy on the solid phase body material are placed in respectively on which position in the said a plurality of somes positions; This proofing unit is characterised in that
Have: to becoming each probe fixed substrate material of detected object, decipher parts according to the some position pattern of given information encryption,
According to from a plurality of the given position patterns that can be applied to this probe fixed substrate material, selecting one carries out a plurality of probes in this probe fixed substrate material, said laying on the solid phase body material;
On this solid phase body material or to being arranged on the framework on this solid phase body material, recording the pattern numbering of the some position pattern that gives this selection in advance;
This proofing unit comprises: the parts that read the pattern numbering of this record; With
According to the pattern that read numbering and the group pattern numbering that gives these a plurality of somes position patterns in advance respectively, come the parts of the specific some position pattern that this probe fixed substrate material is selected.
2. proofing unit; Detect the said a plurality of probes in the probe fixed substrate material that forms on a plurality of somes positions of a plurality of probe stationary of the special bonded of subject matter mass-energy on the solid phase body material are placed in respectively on which position in the said a plurality of somes positions; This proofing unit is characterised in that
Have: to becoming each probe fixed substrate material of detected object, decipher parts according to the some position pattern of given information encryption,
Through as key the reference point location pattern being carried out encrypt treatment to given information, the some position pattern according to new system is produced carries out a plurality of probes in this probe fixed substrate material, said laying on the solid phase body material;
On the said solid phase body material,, record the key that is used to remove said encrypt treatment perhaps to being arranged on the framework on this solid phase body material;
This proofing unit has: read the parts that are used to remove this encrypted secret key; With
Be used to remove encrypted secret key according to what this read, remove the encrypt treatment of in the process that produces this new some position pattern, implementing, come the parts of the specific some position pattern that this probe fixed substrate made is gone out in view of the above.
3. genetic diagnostic device; Use the probe fixed substrate material that on a plurality of somes positions on the solid phase body material, forms to a plurality of probe stationary of the special bonded of subject matter mass-energy; Make the special bonded probe of this subject matter mass-energy is combined on subject substances and the said probe fixed substrate material in the sample; And carry out the detection of institute's bonded subject substances, it is characterized in that:
Have the apparatus structure that in the detection of said bonded subject substances, uses claim 1 or 2 described proofing units.
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